Two novel prevalent polymorphisms in the hormone-sensitive lipase gene have no effect on insulin sensitivity of lipolysis and glucose disposal.

Free fatty acids released during triglyceride lipolysis play an important role in obesity-associated insulin resistance of glucose disposal. Individual sensitivity of lipolysis to the suppressive effect of insulin varies greatly among healthy subjects. It is possible that genetic factors contribute to this variation. Among the many proteins involved in the regulation of lipolysis, hormone-sensitive lipase (HSL) represents a prime candidate for genetic variants contributing to the biological variation of insulin sensitivity of lipolysis. We determined the insulin sensitivity of lipolysis (suppression of isotopically [primed-continuous infusion of d5 glycerol] measured glycerol rate of appearance) and of glucose disposal, using a three-step (n = 20) or standard (n = 53) hyperinsulinemic euglycemic clamp in 73 healthy, unrelated subjects. To assess the possible role of genetic polymorphisms, we directly sequenced the coding region of the HSL gene and the noncoding exon B from these subjects. We identified two silent mutations and three amino acid polymorphisms: Arg262Met (prevalence, 5%), Glu620Asp (prevalence, 31%) and Ser681Ile (prevalence, 22%). The latter two are located in the regulatory domain of HSL but neither had a significant impact on insulin sensitivity of lipolysis or glucose disposal (with and without adjustment for obesity and age as covariates; all P values > 0.20). We conclude that a number of genetic polymorphisms in HSL exist, some of which are highly prevalent. Neither of the polymorphisms we identified in the coding region, however, contributed measurably to the biological variation of insulin sensitivity in our lean, healthy population.

Wrist and hand overuse syndromes.

Overuse syndromes in the wrist or hand can occur from repetitive use of the wrist and hand or from recurrent direct trauma to the hand area. Tendinitis syndromes due to overstretching or shear stress are seen commonly on both the extensor and flexor sides of the wrist. Overuse syndromes also can take the form of neurovascular syndromes, resulting in compression syndromes of the median, ulnar, and superficial branch of the radial nerve in the wrist area and trauma to the ulnar and digital vessels supplying the hand. Treatment in most cases involves rest with splinting, icing, and NSAIDs in acute cases, although surgical decompression is indicated in chronic or recurrent cases.

Nonoperative treatment of ulnar collateral ligament injuries in throwing athletes.

Ulnar collateral ligament injury of the elbow in throwing athletes is a common occurrence, and either operative or nonoperative treatment is an option. The results of operative repairs and reconstructions have been well documented in the literature; however, little information has been reported on the outcome of nonoperative treatment. From 1994 to 1997, we evaluated 31 throwing athletes with ulnar collateral ligament injuries. The purpose of this study was to determine what percentage of athletes could return to their sport without surgical intervention and to identify factors that would predict return to full competition by an athlete treated nonoperatively. The factors studied included acute versus insidious onset of symptoms, the duration of symptoms before treatment, and age. Nonoperative treatment, which included a minimum of 3 months' rest with rehabilitation exercises, allowed 42% of the athletes in our study (N = 13) to return to their previous level of competition. Those who did return did so at an average of 24.5 weeks after diagnosis. No predictive findings obtained either through the patient's history or physical examination were found that would assist the clinician or athlete in predicting the success of nonoperative treatment.

Effects of troglitazone on cellular differentiation, insulin signaling, and glucose metabolism in cultured human skeletal muscle cells.

To determine the immediate effect of thiazolidinediones on human skeletal muscle, differentiated human myotubes were acutely (1 day) and myoblasts chronically (during the differentiation process) treated with troglitazone (TGZ). Chronic TGZ treatment resulted in loss of the typical multinucleated phenotype. The increase of muscle markers typically observed during differentiation was suppressed, while adipocyte markers increased markedly. Chronic TGZ treatment increased insulin-stimulated phosphatidylinositol (PI) 3-kinase activity and membranous protein kinase B/Akt (PKB/Akt) Ser-473 phosphorylation more than 4-fold. Phosphorylation of p42/44 mitogen-activated protein kinase (42/44 MAPK/ERK) was unaltered. Basal glucose uptake as well as both basal and insulin-stimulated glycogen synthesis increased approximately 1.6- and approximately 2.5-fold after chronic TGZ treatment, respectively. A 2-fold stimulation of PI 3-kinase but no other significant TGZ effect was found after acute TGZ treatment. In conclusion, chronic TGZ treatment inhibited myogenic differentiation of that human muscle while inducing adipocyte-specific gene expression. The effects of chronic TGZ treatment on basal glucose transport may in part be secondary to this transdifferentiation. The enhancing effect on PI 3-kinase and PKB/Akt involved in both differentiation and glycogen synthesis appears to be pivotal in the cellular action of TGZ.

The silent PPARgamma exon 6 CAC(His) --> CAT(His) polymorphism does not affect the plasma leptin levels in a collective of first degree relatives of type 2 diabetes patients from South West Germany.

The peroxisome proliferator activated receptors-gamma (PPARgamma) belong to the superfamily of nuclear transcription factors acting as master genes regulating events in adipocyte differentiation. Thus, PPARgamma is a candidate gene for affecting insulin sensitivity and the pathogenesis of insulin resistance. PPARs trigger endocrine response of two important adipose tissue-derived signalling factors, leptin and tumor necrosis factor-alpha. Leptin is the afferent signal in a negative feedback loop regulating adipose tissue mass and energy balance. It generates insulin-like signals for glucose transport and glycogen synthesis via leptin receptors and the PI3-kinase and could, therefore, play a role as a mediator of obesity-related insulin resistance. Recently, a silent substitution in the coding sequence of the PPARgamma2 gene, leading to the substitution of a C by a T in exon 6 (nt 161), was described. In a recent study, it was proposed that mutations in PPARgamma could play a role in individuals who are at increased risk for developing obesity and type 2 diabetes mellitus by influencing leptin levels. We therefore examined the prevalence of the CAC(His) --> CAT(His) mutation in non-diabetic first degree relatives of subjects with type 2 diabetes to determine a possible association of this mutation to leptin levels and insulin sensitivity. 138 probands were characterised by oral glucose tolerance tests, euglycemic-hyperinsulinemic glucose-clamp and by measuring leptin levels. We found 93 (67.4%) probands without the CAC(His) --> CAT(His) substitution and 45 heterozygotes (36.6%). When the whole group was analysed for an association of the mutation with plasma leptin concentration and insulin sensitivity, no statistical significance could be demonstrated. Independently of the mutation, leptin levels were significantly (p<0.001) higher in female subjects.

Management of acute scaphoid fractures.

Scaphoid fractures in the athlete present a dilemma to the treating clinician. Diagnosis of scaphoid fractures should be suspected in any athlete, especially those participating in contact sports, presenting with radial wrist pain. Appropriate imaging studies should be obtained to make a timely and complete diagnosis. Treatment alternatives for acute scaphoid fractures in the athlete include casting and staying out of sports, casting with use of a playing cast, and internal fixation. Displaced unstable fractures and proximal pole fractures should be treated by open reduction and internal fixation. Nondisplaced mid-third fractures are the most common type seen in the athlete. Alternatives of treatment should be carefully explained to the patients and family and the most appropriate treatment employed.

The tumour necrosis factor alpha -238 G --> A and -308 G --> A promoter polymorphisms are not associated with insulin sensitivity and insulin secretion in young healthy relatives of Type II diabetic patients.

AIMS/HYPOTHESIS: Tumour necrosis factor-alpha (TNF-alpha) is believed to influence skeletal muscle insulin resistance. Two G --> A transitions in the promoter region of TNF-alpha at position -238 and -308 have been identified that could play a part in transcriptional regulation of the gene. Insulin resistance is an independent familial trait that predicts the development of Type II (non-insulin-dependent) diabetes mellitus. We investigated the influence on insulin sensitivity and insulin secretion of both polymorphisms in a cohort of young healthy relatives of patients with Type II diabetes. METHODS: We examined 109 first-degree relatives of Caucasian patients with a history of Type II diabetes, who underwent extensive metabolical and anthropometrical phenotyping, and determined the TNF-alpha -238 and -308 G --> A promoter polymorphisms. RESULTS: For the -238 polymorphism, 3 probands (76.1%) were homozygous for the G-allele, 25 probands (22.9%) were heterozygous and 1 proband (0.9%) was homozygous for the A-allele. For the -308 polymorphism, 83 probands (76.1%) were homozygous for the G-allele, 24 probands (22.0%) were heterozygous and 2 probands (1.18%) were homozygous for the A-allele. Probands with and without the polymorphism did not differ in insulin sensitivity (p = 0.78), insulin-concentrations and C-peptide concentrations in oral glucose tolerance tests (p > 0.05). CONCLUSIONS/INTERPRETATION: We could not detect an association between insulin sensitivity or insulin secretion and TNF-alpha promoter polymorphisms in our cohort. The polymorphisms occur at the same frequencies in probands with either low or high insulin sensitivity.

Epidemiology of hand and wrist injuries in sports.

This article addresses the prevalence of various hand and wrist injuries in a variety of sports. Multiple resources and references have been utilized to draw a perception of the types of injuries and the sports with which they are most commonly associated. It is hoped that this article will give the physician a greater understanding of the types of hand and wrist injuries they may expect to encounter in athletes.

Elbow, forearm and wrist injuries in the athlete.

Competitive and recreational athletes sustain a wide variety of soft tissue, bone, ligament, tendon and nerve damage to their upper extremities. Most such injuries are related to direct trauma or repetitive stress, and account for a significant amount of 'down time' for athletes participating in a wide range of sports, particularly those in which the arm is utilised for throwing, catching or swinging. Overuse injuries to the elbow include musculotendinous injuries, ulnar nerve injuries and ligamentous injuries. Osteochondrol lesions of the capitellum and posterior impingement injuries in the joint are frequently seen in athletes as well. Acute traumatic injuries to the elbow include tendon ruptures, elbow dislocations and intra-articular fractures. Forearm overuse injuries in athletes include fracture of the carpal scaphold, fracture of the hook of the hamate, Kienbock's syndrome and pisoquetral syndromes. ligamentous injuries include scapholunate, lunotriquetral and midcarpal instability injuries. Injuries to the distal radio-ulnar joint and triangular fibrocartilage are also quite common in athletes, and require careful evaluation and treatment.

Effects of finger and wrist taping on grip strength.

Taping of the fingers and wrists by professional and collegiate football players has become increasingly prevalent because many players believe taping provides them with increased grip strength. This study was conducted to determine whether taping of the fingers or wrists or both enhances grip strengths in football players. Twenty-five players who self-tape in game situations volunteered for the study. Grip strengths in both taped and untaped conditions (trials) were measured with a hand-held grip dynamometer. Each athlete completed five measurement trials. No statistically significant difference was found between the untaped dominant hand and the dominant hand with the fingers-only taped. There was no significant difference between the untaped nondominant hand and the nondominant hand with the wrist-only taped. The untaped dominant hand was significantly stronger than the taped dominant hand, with mean grip strengths of 142.7 versus 137.8 pounds. The results of these clinical measurements of grip strength showed that, contrary to the perceptions of professional and major college football players, taping of the fingers or wrists or both the fingers and wrists does not improve grip strength.

Internal fixation of acute stable scaphoid fractures in the athlete.

Our study evaluated the results of surgical repair of acute carpal scaphoid fractures in athletes and the time required for the athletes to return to play. Although playing casts are a nonsurgical option, they reduce the effectiveness of the athlete in sports that require maximal manual dexterity; thus, the management of scaphoid fractures is challenging when early return to sports is desired. Twelve athletes with 12 acute midthird scaphoid fractures were treated with Herbert screw fixation. All patients were in-season athletes in sports that precluded the use of a playing cast. Return to sports averaged 5.8 weeks. Nine of the 12 athletes had range of motion equal to the uninjured side. The grip strength was equal to the unaffected side in 10 of the 12 athletes. Clinical and radiographic union was evident in 11 subjects at an average followup of 2.9 years. The healing rates were comparable with other treatment modalities. We concluded that internal fixation of a scaphoid fracture allows safe and early return to sports when a playing cast is not an acceptable option and when an athlete accepts the risks of surgery.

Isolated volar carpometacarpal dislocation of the fifth digit.

McWharter first described volar carpometacarpal dislocations of the fifth digit in 1918. Since then, 14 cases have been reported in the medical literature. Berg and Murphy were first to report a case of ulnopalmar dislocation that was successfully treated with closed reduction and immobilization. Previously reported cases required internal fixation with or without open reduction. We report a fifth carpometacarpal ulnopalmar dislocation, treated with closed reduction and casting.

Effect on knee stability if full hyperextension is restored immediately after autogenous bone-patellar tendon-bone anterior cruciate ligament reconstruction.

We sought to determine if knee stability after autogenous bone-patellar tendon-bone anterior cruciate ligament reconstruction was adversely affected by obtaining immediate full hyperextension. We selected patients based on degree of knee hyperextension. Group 1 (46 men and 51 women), with an average of 10 degrees (range, 8 degrees to 15 degrees) hyperextension, was compared with the randomly selected control Group 2 (70 men and 27 women), which had an average of 2 degrees (range, 0 degrees to 5 degrees) hyperextension. The operative knee in both groups, which underwent similar reconstruction of the injured knee, achieved full passive extension equal to the non-involved knee during the immediate postoperative course. The average KT-1000 arthrometer manual maximum side-to-side differences were 2.4 mm for Group 1 and 2.1 mm for Group 2 (P = 0.13). Seventy-nine patients in Group 1 had KT-1000 arthrometer differences of < or = 3 mm as compared with 85 patients in Group 2. Fourteen patients in Group 1 had KT-1000 arthrometer differences of 4 or 5 mm as compared with eight patients in Group 2. Four patients in each group had KT-1000 arthrometer differences > 5 mm. Evidence suggests that restoring and maintaining immediate full knee hyperextension after this type of reconstruction does not adversely affect the ultimate stability of the knee.

Epidemiology of elbow, forearm, and wrist injuries in the athlete.

Upper extremity injuries in athletes cause pain, impairment of function, and time loss from sport participation. This article briefly discusses the epidemiology of elbow, forearm, and wrist injuries in various athletic endeavors. Included is an overview of the epidemiology of nerve dysfunction, tendon ruptures, fractures about the wrist and forearm, ligamentous injuries of the wrist, distal radioulnar joint injuries, and overuse injuries.

Correlation of remaining patellar tendon width with quadriceps strength after autogenous bone-patellar tendon-bone anterior cruciate ligament reconstruction.

One hundred twenty-one patients were prospectively studied to determine whether the different remaining patellar tendon widths after central 10-mm bone-patellar tendon-bone graft harvest influenced the rate and level of quadriceps strength achieved during rehabilitation. Size of the patellar tendon width, measured at the same location in each patient, ranged from 24 to 35 mm. For this study, patients were grouped according to their remaining tendon size into small (14 to 17 mm; mean, 15.8), medium (18 to 20 mm; mean, 19.2), and large (21 to 25 mm; mean, 22.5) widths. Postoperatively, the patient's isokinetic quadriceps scores were determined at 6 weeks, 3 months, 6 months, and 1 year. At 6 weeks, the small- and medium-width tendon groups were significantly weaker than the large-width tendon group. At 3 months, only the small-width tendon group continued to be significantly weaker than the large-width tendon group. At and beyond 6 months, no statistically significant differences were seen between remaining patellar tendon width groups and their isokinetic quadriceps scores. A constant-sized autogenous patellar tendon graft may be harvested for anterior cruciate ligament reconstruction without compromising ultimate postoperative quadriceps strength recovery.

Wrist problems in the tennis player.

Although wrist injuries in tennis may occur from acute direct trauma, most injuries occur due to chronic overuse. Wrist biomechanics in tennis indicate that a wide range of wrist motion may not be necessary for effective play. The nature of the injury should be established as early as possible with the goals of restoring the wrist to a pain-free stable unit with normal range of motion. A secondary goal is to return the athlete to play as quickly as possible. Key points of the athlete's history are acute or chronic onset, progressive symptoms, and severity of symptoms, i.e., limitation of play. Key points of the physical examination include localization of maximal tenderness, edema, loss of range of motion, and bilateral grip strength. Plain roentgenograms should always be obtained. Specific imaging studies may be indicated and include bone scan, computed tomography, and arthrography. Specific and common wrist tennis injuries are discussed and treatment recommendations are given. Wrist problems in tennis are no uncommon and are responsible for a significant amount of lost playing time. Familiarity with the more common problems will enhance the physician's ability to evaluate and treat these athletes.

Alternative management of midthird scaphoid fractures in the athlete.

The purpose of this retrospective study was to evaluate the effectiveness of two scaphoid fracture treatments in an athletic population. All patients were in-season athletes with a stable, midthird scaphoid fracture incurred in preseason training or early in the season, or athletes who had a consecutive season sport. Group I athletes (N = 18) were treated with immediate open reduction and internal fixation with the Herbert screw. Group II athletes (N = 12) were treated nonoperatively with a playing cast. Return to sports averaged 8.0 weeks for Group I and 4.3 weeks for Group II athletes. Six athletes in Group II were able to return to play immediately with the playing cast. Clinical and radiographic healing averaged 10.8 and 11.2 weeks for Group I and 13.7 and 14.2 weeks for Group II athletes, respectively. In-season athletes with stable midthird scaphoid fractures can safely achieve early return to sport with a playing cast or rigid internal fixation with a Herbert screw. These methods of treatment yield comparable union rates with other series and it appears the athletes are not at increased risk for union failure or nonunion secondary to participation in sports.

Patellar tendon graft reconstruction for midsubstance anterior cruciate ligament rupture in junior high school athletes. An algorithm for management.

Between 1976 and 1988 we treated 75 junior high athletes who had midsubstance ruptures of the anterior cruciate ligament and open physes. Thirty-eight children were initially treated conservatively and later had an intraarticular patellar tendon graft reconstruction, 2 patients underwent extraarticular reconstruction and then later had a patellar tendon graft intraarticular reconstruction, and 20 children had a patellar tendon graft reconstruction initially. In all 60 patients the tibial and femoral tunnels were drilled through the open physes. Minimum followup was 2 years (mean, 4.2). Fifty-five of the 60 children were able to return to their original sports; 5 were active in less strenuous sports. No incidence of abnormal growth related to the intraarticular reconstructive surgery was recorded. Three children tore their anterior cruciate ligament grafts more than 2 years after surgery. Our records showed that conservative treatment of the active junior high athlete with an anterior cruciate ligament rupture failed in each case because of recurrent giving way or meniscal tears. Definitive treatment with an intraarticular autogenous patellar tendon graft reconstruction yielded good to excellent results and eliminated subsequent instability episodes and meniscal tears in our study group.